Hydrochloric Acid → 4-[6-(N-cyclopentylmethylcarbamoyl)-3-[2-(morpholinocarbonyl)ethyl]indol-1-ylmethyl]-3-methoxybenzoic acid

HRID 1198966Notes

Reaction equation

HRID 1198966 reaction equation
[CH:1]1([CH2:6][NH:7][C:8]([C:10]2[CH:18]=[C:17]3[C:13]([C:14]([CH2:40][CH2:41][C:42]([N:44]4[CH2:49][CH2:48][O:47][CH2:46][CH2:45]4)=[O:43])=[CH:15][N:16]3[CH2:19][C:20]3[CH:37]=[CH:36][C:23]([C:24](NS(C4C=CC=CC=4)(=O)=O)=[O:25])=[CH:22][C:21]=3[O:38][CH3:39])=[CH:12][CH:11]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1.BrCC1C=CC(C(OC(C)(C)C)=[O:57])=CC=1OC.Cl>CN(C)C1C=CN=CC=1.N1CCOCC1.O>[CH:1]1([CH2:6][NH:7][C:8]([C:10]2[CH:18]=[C:17]3[C:13]([C:14]([CH2:40][CH2:41][C:42]([N:44]4[CH2:45][CH2:46][O:47][CH2:48][CH2:49]4)=[O:43])=[CH:15][N:16]3[CH2:19][C:20]3[CH:37]=[CH:36][C:23]([C:24]([OH:25])=[O:57])=[CH:22][C:21]=3[O:38][CH3:39])=[CH:12][CH:11]=2)=[O:9])[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14523519Tert-butyl 4-(bromomethyl)-3-methoxybenzoateHCID 19867561N-[4-[6-(N-Cyclopentylmethylcarbamoyl)-3-[2-(morpholinocarbonyl)ethyl]indol-1-ylmethyl]-3-methyoxybenzoyl]benzenesulfonamide

Product 1

HCID 150137814-[6-(N-cyclopentylmethylcarbamoyl)-3-[2-(morpholinocarbonyl)ethyl]indol-1-ylmethyl]-3-methoxybenzoic acidYield 41%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 8083MorpholineSolvent

Procedure

The starting indole was obtained as follows: A solution of 4-[6-(N-cyclopentylmethylcarbamoyl)-3-(2-methoxycarbonylethyl)indol-1-ylmethyl)]-3-methoxybenzoic acid (0.68g)(prepared as described in Example 1, parts (a) through (i)) and 4-(dimethylamino)pyridine (0.17 g) in morpholine (4 ml) was heated at 80° for 48 hours under a nitrogen atmosphere. The reaction was diluted with water and acidified with 10% (v/v) hydrochloric acid. The resultant precipitate was collected by filtration and washed with water. The product was purified by recrystallization from ethyl acetate to give 4-[6-(N-cyclopentylmethylcarbamoyl)-3-[2-(morpholinocarbonyl)ethyl]indol-1-ylmethyl]-3-methoxybenzoic acid as a white powder (0.31 g, 41%); partial NMR (80 MHz, CDCl3) 1.2-1.8(m, 9H, cyclopentyl), 2.70(dd, 2H, CH2NH), 3.15(t, 2H, COCH2), 3.2-3.7(m, 8H, morpholino), 3.92(s, 3H, OCH3), 5.35(s, 2H, ArCH2), 6.58(t, 1H, NH), 7.17(d, 1H), 7.9(s, 1H, H7 -indole).

Workup

  1. filtrationThe resultant precipitate was collected by filtration
  2. washwashed with water
  3. customThe product was purified by recrystallization from ethyl acetate

Sources & evidence

ORD record
ord-e20f233ac859477f92c3e72c352fb979
Source dataset
uspto-grants-1990_02
Patent number
US04898863

Reaction notes

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